The safety and effectiveness of early anti-platelet therapy after alteplase for acute ischemic stroke: A meta-analysis.

BACKGROUND: For acute ischemic stroke patients, there is a risk of reocclusion after intravenous thrombolysis. In theory, early anti-platelet therapy can reduce the risk of vessel reocclusion. Although current guidelines do not recommend routine anti-platelet therapy within 24 h of intravenous thrombolytic therapy, many studies disagreed with it, especially after the emergence of new anti-platelet drugs. It is necessary to conduct a meta-analysis based on high-quality randomized controlled studies to re-evaluate this treatment strategy. METHODS: Literature retrieval was systematically conducted in PubMed, Embase, Cochrane, Web of sicence, clinical trials, CNKI and Wanfang Data, for searching randomized controlled trials (published between January 1, 2000 and April 30, 2020 with no language restrictions) comparing early (within 24 h) with routine (after 24 h) anti-platelet-aggregation therapy after rt-PA intravenous thrombolysis. The primary safety endpoint and primary efficacy indicator are the incidence of symptomatic intracranial hemorrhage and a good prognosis at 90-day (modified Rankin Scale (mRS) score of 0-1 or return to baseline mRS), respectively. We assessed pooled data by use of a random-effects model. FINDINGS: Of the 378 identified studies, only 3 were eligible and included in our analysis (N = 1008 participants). Compared with routine treatment, early anti-platelet-aggregation therapy after rt-PA intravenous thrombolysis in acute ischemic stroke patients did not affect the 90-day efficacy (95% CI 0.97 - 1.32). In terms of safety assessment, the early use of anti-platelet-aggregation drugs after thrombolysis has a neutral effect on the risk of intracranial hemorrhage, symptomatic intracranial hemorrhage, and bleeding from other systemic sites. CONCLUSION: Early anti-platelet therapy after alteplase did not benefit the acute ischemic stroke patients based on the current evidence. However, more clinical trials and statistical evidence are still needed.

Juglone regulates gut microbiota and Th17/Treg balance in DSS-induced ulcerative colitis.

Juglone, mainly isolates from the green walnut husks of Juglans mandshurica, exhibits anti-cancer and anti-inflammaroty activities. But its protection on ulcerative colitis (UC) has never been explored. In this study, we first evaluated whether juglone ameliorated UC, and investigated its effects on gut microbiota and Th17/Treg balance in DSS-induced UC mice model. The model was established by administrating 2.7% DSS for seven days. Juglone was given daily by gavage for ten days, once a day. The disease activity index (DAI) decrease and pathological characteristics improvement demonstrated that the UC in mice was alleviated by juglone. Juglone treatment significantly inhibited the protein levels of IL-6, TNF-α and IL-1ß, improved the protein expression of IL-10. In addition, juglone altered microbial diversity and gut microbiota composition, including the enhancement of the ratio of Firmicutes to Bacteroidota and the abundance of Actinobacteriota, and decrease of the abundance of Verrucomicrobiota. Juglone treatment also inhibited the protein expressions of IL-6, STAT3 and RORγt, meanwhile improved the protein level of FOXP3. Furthermore, juglone inhibited Th17 development and increased Treg generation, beneficial to Th17/Treg balance. Together, we herein provided the first evidence to support that juglone, especially the high dose, possibly protected mice against UC by modulating gut microbiota and restoring Th17/Treg homeostasis.

Scutellaria baicalensis Georgi polysaccharide ameliorates DSS-induced ulcerative colitis by improving intestinal barrier function and modulating gut microbiota.

The aim of this study was to investigate the effect of a polysaccharide from Scutellaria baicalensis Georgi on UC. Gut microbiota dysbiosis is a worldwide problem associating with ulcerative colitis. One homogeneous polysaccharide, named SP2-1, was isolated from Scutellaria baicalensis Georgi. SP2-1 comprised mannose, ribose, rhamnose, glucuronic acid, glucose, xylose, arabinose, fucose in the molar ratio of 5.06:21.24:1.00:20.25:3.49:50.90:228.77:2.40, with Mw of 3.72 × 106 Da. SP2-1 treatment attenuated body weight loss, reduced DAI, ameliorated colonic pathological damage, and decreased MPO activity of UC mice induced by DSS. SP2-1 also suppressed the levels of proinflammatory cytokines. Additionally, the intestinal barrier was repaired due to the up-regulated expressions of ZO-1, Occludin and Claudin-5. SP2-1 remarkably enhanced the levels of acetic acid, propionic acid, and butyric acid in DSS-treated mice. Furthermore, as compared with model group, the abundance of Firmicutes, Bifidobacterium, Lactobacillus, and Roseburia were significantly increased with SP2-1 treatment. And SP2-1 could significantly inhibit the levels of Bacteroides, Proteobacteria and Staphylococcus. In conclusion, SP2-1 might serve as a novel drug candidate against UC.

Comparison of the analgesic efficacy of preemptive and preventive tramadol after lumpectomy.

The aim of this study was to investigate the analgesic efficacy of tramadol administrated preemptively or preventively in the earlier period of lumpectomy. Four hundred American Society of Anesthesiologists (ASA) physical status I-II patients, undergoing lumpectomy, were screened and 317 were randomly assigned into one of two groups. In the preemptive tramadol (n = 158) group, patients received an iv injection of tramadol 100 mg 15 min before operation. The preventive group (n = 159) received the same dose of tramadol 15 min before the end of the operation. Pain intensity at rest, overall satisfaction score, morphine consumption and side effects were recorded. A total of 299 patients completed the study. Preemptive and preventive subjects experienced similar analgesic effect and feeling of satisfaction at the first 24 h after surgeries. The similar amount of additional morphine was consumed [4.6 mg (95% CI 1.5-7.2) vs. 4.1 mg (95% CI 1.2-6.3), p = 0.811]. No intergroup difference was observed in the incidence of side effects. In conclusion, preemptive and preventive administration of tramadol expressed analgesia of similar efficacy up to 24 h after lumpectomy. The additional morphine requirement, the overall satisfaction and the frequency of side effects all did not display significant difference between the two groups. This implies that the administration of tramadol either before the start or before the end of the surgical procedures all can produce effective postoperative analgesia.

[mRNA expression and activity of ADAM17 in hippocampus after chronic cerebral hypoperfusion: experiment with aged rats].

OBJECTIVE: To explore the effect of alpha-secretase on the pathogenesis of cognitive impairment following cerebral ischemia. METHODS: Forty-eight 12~16-months-old Wistar rats were randomly divided into 2 equal groups: hypoperfusion group, undergoing permanent occlusion of bilateral common carotid arteries to mimic cerebral hypoperfusion, and sham-operation group. Each group was further divided into 1, 2, 4, and 16 week subgroups. Y-maze test was conducted before operation and at different time points as mentioned above to examine the spatial learning and memory ability. The rats tested by Y-maze were killed with their hippoccampi taken out. Realtime PCR was used to assay the mRNA expression of a disintegrin and metalloproteinase (ADAM)-17 representing alpha-secretase in the hippocampus, and fluorescence spectrometry was applied to measure activity thereof. RESULTS: The numbers of electric stroke since 2 weeks after hypoperfusion were significantly higher than that before hypoperfusion in the same group and those of the sham-operation group (P < 0.05 or P < 0.01). The mRNA expressions of hippocampal ADAM17 of the hypoperfusion subgroup 2, 4, and 16 weeks after operation were 0.78 +/- 0.03, 0.78 +/- 0.02, and 0.54 +/- 0.03 respectively, all significantly lower than those of the sham-operation group (1.12 +/- 0.05, 0.99 +/- 0.04, and 1.01 +/- 0.04 respectively, all P < 0.01). The average fluorescence values of hippocampal alpha-secretase 1, 2, 4, and 16 weeks after hypoperfusion of the hypoperfusion group were 33,880 +/- 1086, 37,496 +/- 817, 32,295 +/- 864 and 30,069 +/- 1111, respectively, all significantly lower than those of the sham-operation group (39 497 +/- 838, 39 802 +/- 1052, 40,137 +/- 776, and 39,894 +/- 1076 respectively, all P < 0.01). CONCLUSION: The mRNA expression of ADAM17 that represents alpha-secretase in the hippocampus is down-regulated and the activity of alpha-secretase is decreased after chronic cerebral hypoperfusion. That may subsequently result in accumulation of beta amyloid precursor protein, substrate of alpha-secretase, (APP), and then activate the other pathway cleaving APP, i.e., the pathway by beta secretase. At last, the production of beta amyloid protein in brain after chronic cerebral hypoperfusion increases and impairs the memory.